Heart rate variability correlates with the effect of sulforaphane on calorie-induced inflammation in healthy participants: a randomized placebo-controlled study

Background & Aims: The role of nutrition in modulating the inflammatory response is increasingly recognized. The phytonutrient sulforaphane shows promise for clinical use due to its effect on inflammatory pathways, favorable pharmacokinetic profile, and high bioavailability. The inflammatory status has been linked to autonomic activity, which can be assessed by the study of heart rate variability (HRV). However, monitoring of HRV for assessment of inflammation in humans has hardly been used. We investigated the potential of HRV as a non-invasive tool to monitor inflammation induced by the caloric load and assessed the effects of sulforaphane on caloric load-induced inflammation in healthy participants. Methods: In this double-blind, crossover, randomized, placebo-controlled trial twelve healthy participants (26.9 (3.6) years) were administered 25 mg of sulforaphane, or placebo followed over 90 min by the standardized high-calorie drink PhenFlex given to induce an inflammatory response. Levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 were measured in plasma before and two hours after the PhenFlex challenge. Changes in the autonomic function were assessed by HRV on four timepoints. Results: The caloric challenge triggered a significant increase in total power (TP) (P = 0.028) and very low frequency (VLF) component (P = 0.013) 30 min after its administration. Those changes were followed by reduction of TP (P = 0.028) and low frequency (LF) component (P = 0.005), suggesting marked decrease in the sympathetic activity two hours after the caloric load. When sulforaphane was given prior to the caloric challenge, decreased parasympathetic activity was observed via a reduction of RMSSD (P = 0.007), pNN50 (P = 0.013) and HF (P = 0.047). In addition, sulforaphane elicited a pro-inflammatory response as measured by the change of hs-CRP with caloric exposure (sulforaphane 2.7 (4.2) vs. placebo -1.8 (3.1) ng/mL, P = 0.048). The pro-inflammatory effect of sulforaphane was associated with vagal withdrawal and sympathetic dominance as suggested by correlations between the changes in hs-CRP and HF (rs = -0.68, P = 0.029) as well as LF/HF (rs = 0.56, P = 0.093) components assessed before and two hours after the PhenFlex challenge. Conclusions: Monitoring of HRV might be a sensitive tool to follow activity of the inflammatory response in various clinical conditions. The standardized caloric PhenFlex challenge induced significant changes in the autonomic regulation in healthy young individuals. Administration of sulforaphane prior to the caloric challenge caused a pro-inflammatory effect which was accompanied by vagal withdrawal and sympathetic dominance. Trial registration number: NCT05146804 at www.clinicaltrials.gov.